University of Tokyo

About: University of Tokyo is a education organization based out in Tokyo, Japan. It is known for research contribution in the topics: Population & Gene. The organization has 134564 authors who have published 337567 publications receiving 10178620 citations. The organization is also known as: Todai & Universitas Tociensis.

CD8 + effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity

Abstract: Inflammation is increasingly regarded as a key process underlying metabolic diseases in obese individuals. In particular, obese adipose tissue shows features characteristic of active local inflammation. At present, however, little is known about the sequence of events that comprises the inflammatory cascade or the mechanism by which inflammation develops. We found that large numbers of CD8(+) effector T cells infiltrated obese epididymal adipose tissue in mice fed a high-fat diet, whereas the numbers of CD4(+) helper and regulatory T cells were diminished. The infiltration by CD8(+) T cells preceded the accumulation of macrophages, and immunological and genetic depletion of CD8(+) T cells lowered macrophage infiltration and adipose tissue inflammation and ameliorated systemic insulin resistance. Conversely, adoptive transfer of CD8(+) T cells to CD8-deficient mice aggravated adipose inflammation. Coculture and other in vitro experiments revealed a vicious cycle of interactions between CD8(+) T cells, macrophages and adipose tissue. Our findings suggest that obese adipose tissue activates CD8(+) T cells, which, in turn, promote the recruitment and activation of macrophages in this tissue. These results support the notion that CD8(+) T cells have an essential role in the initiation and propagation of adipose inflammation.

Lethal effect of the anti-Fas antibody in mice

Abstract: DURING mammalian development, many cells are programmed to die1,2 most mediated by apoptosis3. The Fas antigen4 coded by the structural gene for mouse lymphoproliferation mutation (lpr)5,6, is a cell surface protein belonging to the tumour necrosis factor/nerve growth factor receptor family7,8, and mediates apoptosis7. The Fas antigen messenger RNA is expressed in the thymus, liver, heart, lung and ovary8. We prepared a monoclonal antibody against mouse Fas antigen, which immunoprecipitated the antigen (Mr 45K) and had cytolytic activity against cell lines expressing mouse Fas antigen. We report here that staining of mouse thymocytes with the antibody indicated that thymocytes from the wild-type and lprcg mice expressed the Fas antigen, whereas little expression of the Fas antigen was found in lpr mice. Intraperitoneal administration of the anti-Fas antibody into mice rapidly killed the wild-type mice but neither lpr nor lprcg mice. Biochemical, histological and electron microscope analyses indicated severe damage of the liver by apoptosis. These findings suggest that the Fas antigen is important in programmed cell death in the liver, and may be involved in fulminant hepatitis in some cases.

Mitochondrial DNA Mutations, Oxidative Stress, and Apoptosis in Mammalian Aging

Abstract: Mutations in mitochondrial DNA (mtDNA) accumulate in tissues of mammalian species and have been hypothesized to contribute to aging. We show that mice expressing a proofreading-deficient version of the mitochondrial DNA polymerase g (POLG) accumulate mtDNA mutations and display features of accelerated aging. Accumulation of mtDNA mutations was not associated with increased markers of oxidative stress or a defect in cellular proliferation, but was correlated with the induction of apoptotic markers, particularly in tissues characterized by rapid cellular turnover. The levels of apoptotic markers were also found to increase during aging in normal mice. Thus, accumulation of mtDNA mutations that promote apoptosis may be a central mechanism driving mammalian aging.

Orbital Physics in Transition-Metal Oxides

Abstract: An electron in a solid, that is, bound to or nearly localized on the specific atomic site, has three attributes: charge, spin, and orbital. The orbital represents the shape of the electron cloud in solid. In transition-metal oxides with anisotropic-shaped d-orbital electrons, the Coulomb interaction between the electrons (strong electron correlation effect) is of importance for understanding their metal-insulator transitions and properties such as high-temperature superconductivity and colossal magnetoresistance. The orbital degree of freedom occasionally plays an important role in these phenomena, and its correlation and/or order-disorder transition causes a variety of phenomena through strong coupling with charge, spin, and lattice dynamics. An overview is given here on this "orbital physics," which will be a key concept for the science and technology of correlated electrons.

Genetics of rheumatoid arthritis contributes to biology and drug discovery

Abstract: A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2, 3, 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci6 and pathway analyses7, 8, 9—as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes—to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.